Pharmacology

This illustration represents, from left to right, the five main areas of pharmacology, which are the brain, kidneys, metabolism, free radicals, mitochondria and plasma membrane. The rainbow and the prism represent photobiology and precipitate vessels biochemistry

Pharmacology (from the Greek, pharmacon (φάρμακον), drug and logos (λόγος), science) is the branch of pharmaceutical sciences that study the history, origin, biophysiochemical properties, presentation, physiological effects, mechanisms of action, absorption, distribution, biotransformation, excretion and therapeutic use, among other biological activities, of substances Chemicals that interact with living organisms. Pharmacology studies how the drug interacts with the organism, its actions, effects and properties. In a stricter sense, pharmacology is considered as the study of drugs, whether they have beneficial or toxic effects. Pharmacology has clinical applications when substances are used in the diagnosis, prevention and treatment of a disease or for the relief of its symptoms.

History

The origins of clinical pharmacology go back to the Middle Ages, with pharmacognosy and Avicenna's Canon of Medicine, Peter of Spain's Commentary on Isaac, and Juan de San Amand's Commentary on Nicholas' Antedotary. Early pharmacology focused on herbalism and natural substances, mainly plant extracts. Medicines were compiled in books called pharmacopoeia. Crude drugs have been used since prehistoric times as a preparation of substances from natural sources. However, the active ingredient in crude drugs is not purified and the substance is adulterated with other substances.

Traditional medicine varies across cultures and can be specific to a particular culture, such as traditional Chinese, Mongolian, Tibetan, and Korean medicine. However, much of this has been regarded as pseudoscience. Pharmacological substances known as entheogens may have spiritual and religious use and historical context.

In the 17th century, the English physician Nicholas Culpeper translated and used pharmacological texts, in which he detailed the plants and the conditions they might treat. In the 18th century, much of clinical pharmacology was established by the work of William Withering.

Pharmacology as a scientific discipline did not advance further until the middle of the 19th century, in the midst of the great biomedical revival of that period. Before the second half of the 19th century, the remarkable potency and specificity of drugs such as morphine and quinine were vaguely explained. and with reference to extraordinary chemical powers and affinities with certain organs or tissues.

The first department of pharmacology was created by Rudolf Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produce their effects. Subsequently, the first department of pharmacology in England was created in 1905 at University College London.

Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to clinical contexts. therapeutic. The advancement of research techniques promoted pharmacological research and its understanding. The development of the organ bath preparation, where tissue samples are connected to recording devices (such as a myograph) and physiological responses are recorded after drug application, allowed analysis of the effects of drugs on patients. tissues. The development of the ligand binding assay in 1945 allowed quantification of the binding affinity of drugs on chemical targets. Modern pharmacologists use techniques from genetics, molecular biology, biochemistry, and other advanced tools to transform information about molecular mechanisms and targets into targeted therapies against diseases, defects, or pathogens, and to create methods for preventive care, diagnosis, and ultimately, personalized medicine.

Divisions

The discipline of pharmacology can be divided into many sub-disciplines, each with a specific focus.

Body Systems

Pharmacology can also focus on specific systems that comprise the body. The body systems divisions study the effects of drugs on different body systems. These include neuropharmacology, in the central and peripheral nervous system; Immunopharmacology in the immune system. Other divisions include cardiovascular, renal, and endocrine pharmacology. Psychopharmacology is the study of the effects of drugs on the psyche, mind, and behavior, including the behavioral effects of psychoactive drugs. He incorporates approaches and techniques from neuropharmacology, animal behavior, and behavioral neuroscience, and is interested in the behavioral and neurobiological mechanisms of action of psychoactive drugs. The related field of neuropsychopharmacology focuses on the effects of drugs on the overlap between the nervous system and the psyche.

Pharmacometabolomics, also known as pharmacometabolomics, is a field that stems from metabolomics. It consists of the direct measurement of metabolites in the body fluids of an individual, in order to predict or evaluate the metabolism of pharmaceutical compounds, and to better understand the pharmacokinetic profile of a drug [1]. Pharmacometabolomics can be applied to measure metabolite levels after drug administration, in order to monitor drug effects on metabolic pathways. He also studies the effect of microbiome variations on drug disposition, action, and toxicity, as well as the interaction between drugs and the gut microbiome. Pharmacogenomics is the application of genomic technologies for drug discovery and further characterization of drugs related to the entire genome of an organism. For pharmacology with respect to individual genes, pharmacogenetics studies how genetic variation gives rise to different responses to drugs. Pharmacoepigenetics studies the underlying epigenetic marking patterns that lead to variations in an individual's response to medical treatment.

Clinical Practice and Drug Discovery

A toxicologist working in a lab.

Pharmacology can be applied within the clinical sciences. Clinical pharmacology is the basic science of pharmacology that focuses on the application of pharmacological principles and methods in clinical medicine and in patient care and outcomes. An example of this is dosage, which is the study of how drugs are dosed.

Pharmacology is closely related to toxicology. Both pharmacology and toxicology are scientific disciplines that focus on understanding the properties and actions of chemicals. However, pharmacology emphasizes the therapeutic effects of chemicals, usually drugs or compounds that could become drugs, while toxicology is the study of the adverse effects of chemicals and risk assessment.

Pharmacological knowledge is used to advise drug therapy in medicine and pharmacy.

Fate of drugs in the body

Any substance that interacts with a living organism can be absorbed by it, distributed by different organs, systems or body spaces, modified by chemical processes and finally expelled.

Pharmacology studies the processes in the interaction of drugs with humans and animals called "LADME" which, in temporal order, are the following:

• liberation
• absorption
• distribution
• metabolism
• excretion

The study of these processes is known as pharmacokinetics. From the interaction of all these processes, pharmacology can predict the bioavailability and elimination half-life of a drug in the body given a route of administration, a dose, and an administration interval.

For the drug to exert its action on this target, it must generally be transported through the bloodstream.

Absorption

To reach blood circulation, the drug must cross some barrier given by the route of administration, which can be: cutaneous, subcutaneous, respiratory, oral, rectal, muscular, otic route, ophthalmic route, sublingual route. Or it can be inoculated directly into the circulation through the intravenous route. Pharmacology studies the plasma concentration of a drug in relation to the time elapsed for each route of administration and for each possible concentration, as well as the different forms of use of these routes of administration.

Distribution

Once in the bloodstream, the drug, due to its characteristics of size and molecular weight, electrical charge, pH, solubility, protein binding capacity, is distributed among the different body compartments. Pharmacology studies how these characteristics influence the increase and decrease of drug concentration over time in different systems, organs, tissues and body compartments, such as in the cerebrospinal fluid, or in the placenta, etc.

Metabolism or biotransformation

Many drugs are transformed in the body due to the action of enzymes.

This transformation may consist of degradation; (oxidation, reduction or hydrolysis), where the drug loses part of its structure, or in the synthesis of new substances with the drug as part of the new molecule (conjugation).

The result of the biotransformation can be the complete or partial inactivation of the effects of the drug, the increase or activation of the effects, or the change for new effects depending on the characteristics of the synthesized substance.

Pharmacology studies the mechanisms by which these transformations occur, the tissues in which they occur, the speed of these processes and the effects of the drugs themselves and their metabolites on the same enzymatic processes.

Excretion

Finally, the drug is eliminated from the body through some excretory organ. Mainly there is the liver and kidney, but the skin, salivary and tear glands are also important. When a drug is sufficiently water soluble, it is diverted into the bloodstream, through which it reaches the kidneys and is eliminated by the same processes as urine formation: glomerular filtration, tubular secretion, and tubular reabsorption. If the drug, on the other hand, is lipid soluble or too large to pass through the renal capillaries, it is excreted in the bile, reaching the large intestine where it can undergo enterohepatic recirculation or be eliminated in the feces.

Pharmacology studies the form and rate of clearance of drugs and their metabolites by the different excretory organs, in relation to the plasma concentrations of the drug.

The effect of drugs, after their administration, depends on the variability in absorption, distribution, metabolism and excretion.

For the drug to reach its site of action, the following factors must be considered:

• Rate and degree of absorption from the application site.
• Rate and degree of distribution in fluids and body tissues.
• Biotransformation rate to active or inactive metabolites.
• Excretion rate.

Action of drugs on the body

The study of the set of sensitive and/or measurable effects that a drug produces in the organism of the human being or animals, their duration and their temporal course, is called pharmacodynamics.

For this study, pharmacology understands the system, organ, tissue or cell that receives the drug or object of the substance under analysis, as having receptors with which the substance interacts.

The interaction between substance and receptor is an important field of study, which, among other aspects, analyzes:

• Quantification of drug/receptor interaction.
• Receptor regulation, whether to increase, decrease or change in response level.
• Relationship between dose and response.

Pharmacodynamics defines and classifies drugs according to their affinity, potency, efficacy, and relative effects. Some of the important indices of these definitions are the ED50 and LD50, which are the minimum doses necessary to achieve the desired effect and death respectively, in 50% of a given population. The relationship between these values is the therapeutic index.

According to the type of predominant effect of a drug, pharmacodynamically they are classified as:

• Pharmacological agonists, if it produces or increases the effect.
• Pharmacological antagonists, if the effect is diminished or eliminated.

Pharmacodynamics also studies the variability in the effects of a substance depending on individual factors such as: age, race, pregnancy, pathological states, etc.

There is also a special field of study of the pharmacological effects of substances during pregnancy.

In humans, the effects of drugs on the embryo and fetus is a field of intense study.

Branches of Pharmacology

• Pharmacokinetics: the study of the physical-chemical processes that a drug suffers when given or incorporated into an organism. These processes would be liberation, absorption, distribution, metabolization and elimination.
• Pharmacodynamics: science that studies the mechanism of action of drugs, that is, studies how the biochemical and physiological processes within the organism are affected by the presence of the drug.
• Biopharmacy: the study of the bioavailability of drugs.
• Pharmacognosis: study of medicinal plants and drugs derived from them.
• Pharmaceutical chemistry: studies drugs from a chemical point of view, including the discovery, design, identification and preparation of biologically active compounds, the interpretation of their mode of interaction at a molecular level, the construction of their structure-activity relationship and the study of their metabolism.
• Gallic Pharmacy or Pharmacotecnia: branch entrusted to the formulation of drugs as medicines.
• Posology: the study of drug dosage.
• Toxicology: the study of the harmful or toxic effects of drugs.
• Clinical pharmacology: evaluates the effectiveness and safety of drug therapy.
• Pharmacovigilance: is a discipline that allows post-marketing surveillance of medications to detect, prevent and report adverse reactions in patient groups.
• Chronopharmacology: The study of the correct administration of drugs according to the circadian cycle of the human being, in order to maximize efficacy and decrease the collateral effects.

Therapeutic margin and index

It is a practical fact that is known to all that by increasing the dose of a certain drug, the risk of producing toxic or adverse phenomena increases.

To avoid such a situation, experimental and clinical pharmacologists carry out an evaluation of the safety of the drug, in order to guarantee that the desired pharmacological effect is achieved with the dose used, reducing the risk of poisoning.

The simplest and easiest evaluation is known as Therapeutic Range, which is the dose range that oscillates between the minimum dose and the maximum therapeutic dose. From the foregoing it follows that a medication can be dosed within this range, making no sense in administering a dose higher than the maximum therapeutic dose, since with it we would not obtain a superior effect, and we are approaching that dose that can be toxic..